In general, the biological effect of proteins is modulated by various mechanisms of post-translational modifications. Specifically, it has been shown that methylation, acetylation, glycosylation, phosphorylation, or the like, is involved in the regulation of functions or structures of proteins. Among these post-translational modifications, phosphorylation is an important mechanism related to modulation of many functions such as intracellular signal transduction, cell cycle, and cell death, or the like. For example, it is thought that more than one-third of the intracellular proteins in mammalian cells are phosphorylated.
Proteins are phosphorylated by the action of protein kinases. In general, a protein kinase catalyzes a reaction of bonding a phosphate group to a specific site of a specific substrate protein. That is to say, proteins are phosphorylated on specific amino acid residues. Thus, protein kinases can be classified as follows based on amino acids at a site to be phosphorylated.
Serine/threonine kinase (Ser/S or Thr/T residue is phosphorylated)
Tyrosine kinase (Tyr/Y is phosphorylated)
Human CDC7 that is one of the serine/threonine kinases is a protein kinase involved in the start of DNA replication during the cell cycle. Specifically, it is thought that with phosphorylation of MCM (Minichromosome maintenance) protein by CDC7, CDC45 and DNA polymerase are recruited to DNA and the DNA replication starts. The phosphorylation action of CDC7 needs a cofactor. For example, ASK is identified as a cofactor that activates the phosphorylation action of CDC7.
It is thought that CDC7 involved in DNA replication can be an important target for cell proliferation diseases such as cancers. In other words, when the DNA replication necessary for the cell proliferation can be controlled by inhibiting CDC7, the cell proliferation may be suppressed. Various compounds, which have an inhibitory action against protein kinase including CDC7, have been reported to date (Patent Documents 1 to 5).    [Prior Art Documents]    [Patent Documents]    [Patent Document 1] WO2007/071621    [Patent Document 2] WO2007/096334    [Patent Document 3] WO2007/110344    [Patent Document 4] WO2007/124288    [Patent Document 5] WO2008/046982